Autism and Music

Autism Spectrum disorders affect about 6 in every 1,000 people with varying severities. The prevalence has been drastically increasing since the 1980’s, but most people believe that is not due to an actual increase in the disorder but simply a change in diagnostic criteria.
Autism starts affecting children before the age of three. It is characterized by difficulty with social interactions, repetitive behaviors, and difficulty in acquiring and using language. About 0.5% to 10% of autistic individuals are called autistic savants. They are extremely gifted in one skill set or talent. Though scientists are not in agreement with the causes of autism, there are many theories that dominate the general discourse. It is commonly assumed to be a combination of environmental and genetics with differing emphasis between the two. The research that is compelling for the genetics autism paradigm involves studies of identical twins which proved that there was a 60% chance that the twin of an autistic child would develop autism. These results are staggering considering that .6% of the population has autism and fraternal twins showed no significant increase in autism prevalence.
Further, many researchers have found physical irregularities in several parts of the brain including the levels of serotonin in the brain. Specifically, research centers called “Centers of Excellence in Autism Research” have shown that connections in the brain are often impaired in autistic children. “Research is now being conducted all over the world to determine specific genes that increase the likelihood of someone developing autism. A group known as the International Molecular Genetic Study of Autism Consortium, which includes clinicians and researchers from the USA, UK, France, the Netherlands, Denmark, Italy, and Greece, has pinpointed four chromosomes which they believe play critical roles in autism. The chromosomes they identified are numbers 2, 7, 16 and 17. The evidence for involvement of chromosomes 2 and 7 is particularly strong as these had also been previously identified by other independent researchers (2,3,4,5). Chromosome 7 is known to be associated with many language disorders and chromosome 2 plays an important role in early brain development. These findings are further demonstrated by research showing dyslexia patients also have abnormalities on these chromosomes. This is not surprising as dyslexia also produces deficits in learning ability and information processing in the brain”
The problem with autism is something that we take for granted. Most of us learn how to make sense of our environment through an unconscious ability to combine our sensory information. What we hear, see, feel and know all merge to create spatial maps that allow us to understand our relative place in space. In childhood, we learn how to put our senses together to respond more efficiently to impediments presented to us in our environment. Children with autism have trouble learning to do this. They have greater difficulty creating a synthesis of all the sensory information and therefore have more difficulty responding to the environmental impediments. Sensory integration therapy is a type of occupational therapy that places children in a room specifically designed to stimulate and challenge all of the senses. This therapy is based on the assumption that the child is either overstimualted or understimulated by the environment. Specifically music therapy seeks to stimulate the auditory processing in autistic children so that the overall sensory integration will be more efficient. Music therapy seeks to regulate a common trend in autism; acute lack of total sensory integration. This is reflected and materialized in many ways in the brain.

Auditory Processing of Music
The majority of symptoms in children and adults include attention deficits, learning disabilities, autism, obsessive-compulsive disorder, depression, anxiety, chronic pain and many more are all directly a result of an imbalance of electrical activity in the brain. There are many environmental factors that can produce an imbalance of electrical activity and function of the two sides of the brain documented as either an increase of activity on one side or a decreased activity on the other.
Adverse activity is the right hemisphere which autism is expected to be specifically stimulated by low frequency tones, negative or downbeat music. Specifically, autism is a common sensory processing disorder (SPD). In children with autism, sensory integration is very difficult to accomplish. Music therapy can work as a way to increase the integration of the main sensory areas. The sensory system is broken up into three main areas: the tactile, vestibular, and the proprioceptive sense. The tactile system is your sense of touch. The vestibular system is responsible for movement and the body’s position in space. The proprioceptive system deals with muscles and joints. There are other sensory systems but they are not as commonly associated with sensory dysfunction.
The vestibulocochlear system informs us of sound, movement and orientation of space. The cochlear portion of the system turns sound or vibration into electrochemical messages that are relayed throughout the central nervous system and is critical to auditory processing. The vestibular portion serves to provide stabilization, influences attention and arousal, posture, movement, thus being critical to sensorimotor integration. It is the integration of our senses that allows us to understand what we are experiencing in our world.
Specifically, the vestibular system contributes to our balance and our sense of spatial orientation that provides input about movement and equilibrioception. (equilibrioception is what experiencial information from the vestibular system is called.) It is anatomically joined with cochlear system, and the systems lie closely together throughout the nervous system and together elaborate the general labyrinth of the inner ear.



Further, there is a profound connection between vestibular functioning and language processing. This allows for many close neuronal associations with auditory processing and language. The vestibular system sends signals primarily to the neural structures that control our eye movements, and to the muscles that keep us upright.
Decreased vestibular processing can impact on the area of speech and language development, particularly auditory processing. It is associated with autistic disorder, which are generally categorized by decreased electrical neurotransmitting activity. Research has found that therapy to improve the function of the vestibular system can also result in improved language development.


Musical Processing and Emotional Understanding
Vestibular complications are not the only ways that music can affect autism. A benefit to music therapy for autistic children aids them in verbal communication and social interaction deficits. A proposed study by Molnar Szakacs and Overy wants to compare musical processing on a neurological basis to communication, language and action. This is determined by the mirror neuron system, which allows us to abstract musical sounds similar to the ways in which humans form language when speaking and interacting. “The mirror neuron system has been proposed as a mechanism allowing an individual to understand the meaning and intention of a communicative signal by evoking a representation of that signal in the perceivers own brain “(p.235.) Spatial maps created in the brain, specifically the parietal lobe, are influenced by these mirror neurons and contribute to an overall understanding of actions and intentions. Essentially, mirror neurons enable humans to understand emotions through facial and body expressions.
Music is closely connected with motor activity. Producing music involves developed spatial maps and a physical understanding of vibrations and sounds. The mirror neuron system that allows someone to understand musical experiences is the same set of neurons that is present in motor functioning and mapping. There have been recent neuro-imaging studies that show that people with musical expertise have a change in their fronto-parietal mirror neuron system. Music is also inherently similar to language. Music is pitches composed into symphonies the way that language is words composed into novels.
The proposed study by Molnar Szakacs emphasizes the important connection between an understanding of language with an understanding of music. This is further emphasized by research conducted on other language disorders like dyslexia. The main point that Molnar Szakacs intends to look at is if language and music are so similar and if they are dictated by similar mirror neural patterns, then why can’t autistic savants with high pitch sensitivity understand facial emotions and social communications?
Mirror neurons are cells that enable normally developing people to decipher meaning and intention in actions as well as replicate those actions. Autistic children are typically noted to have a decreased or altered mirror neural system. This affects the ways in which the limbic system, which is responsible for emotions, interacts with those mirror neurons. This comes back to the point that these same mirror neurons are involved in the understanding of music. 

Music Based Therapies

So it makes sense that a program that would stimulate and help to integrate the cochlear and vestibular systems might be very helpful for the autistic child’s emotional understanding. This does not present a cure for autism, but The Listening Program (TLP) can be an effective intervention for children on the autistic spectrum.
TLP is a music-based sound stimulation program that currently consists of 8 one hour audio CD’s that contain specially processed classical music and nature sounds plus a 112 page guidebook. Listening sessions are typically fifteen minutes in length, done once or twice a day, five days a week, using high quality stereo headphones.

1- Increases engagement- The individuals experience an improvement in their self-image and an improved sense of their body in space. This enables them to feel more comfortable interacting with their surroundings. They show an increase in the toleration and need for physical contact. There is also an increase in attentiveness and initiation of eye contact.
2- Emerging Skills- When used in conjunction with other forms of therapy, it allows for better integration of the motor and sensory systems which in turn leads to a faster rate of skill acquisition.
3- Auditory Processing- It improves the accuracy and speed at which individuals process sound. This leads to better overall communication skills.
4- Reduced Sound Sensitivity- Many autistic individuals experience hypersensitivity to sounds because their nervous system is unable to regulate the sensory input. This program helps the nervous system be able to better process sensor info, which reduces sound sensitivity.

Obesity: Reviving the Promise of Leptin

The History of Leptin

• Discovered by Douglas Coleman (The Jackson Laboratory, Bar Harbor, Maine)

• Parabiosis of normal mice with either diabetic or overweight mice.

• Found that there was a "satiety factor" circulating in the blood. Hypothesized that db mice lacked the receptor to the factor, while ob mice did not produce it.
  

• It could not be extracted from the blood because it was present in tiny amounts. However, the gene responsible for it was eventually isolated and the "satiety factor", leptin, was produced in a lab. The leptin gene is spliced into bacteria and the bacteria sets to work producing the protein.
  

• By the mid 1990s it was greeted as a possible miracle cure for the rising obesity epidemic. 1995 New York Times headline read: "Researchers find hormone causes a loss of weight". Leptin is discussed as a "magic bullet", which would hopefully "change the image of obesity, helping people to see it not as a punishment for gluttony but rather as a metabolic disorder, treatable with a remedial hormone just as diabetes is treated with insulin."

• By the end of 90s none of the new research had panned out. All experiments that had been done on obese humans had found that leptin rarely caused weight loss, and if it did it was only temporary. New York Times headline from 1999 read: "Hormone that slimmed fat mice disappoints as panacea in people". Researchers determined that obese people were somehow resistant to leptin, so it was not effective in their brain.

• Since then most research has focused on understanding the metabolic pathways of leptin, and little thought has been given as to how it might be used as a treatment for obesity.

How is Appetite Controlled?

• Hypothalamus is the main organ involved in regulation of appetite; specifically the arcuate nucleus (situated at the base).

• The neurons involved primarily employ serotonin as a neurotransmitter, although neuropeptide Y and Agouti-Related peptide are also involved.

• The hypothalamus uses Ghrelin, Leptin, Insulin and PYY as markers to influence how hungry we feel.

• Ghrelin is excreted by the stomach may also be produced in the brain. Causes feelings of hunger and is associated with regular meal times. Ghrelin levels rise immediately before a meal and fall sharply after eating.
  

• Ghrelin Factoids: Those suffering from anorexia nervosa have higher blood levels of ghrelin. - Individuals who have undergone gastric bypass surgery produce less ghrelin. - Ghrelin acts not only on neurons in the arcuate nucleus but also activates reward circuitry in the brain associated with dopamine.

• Leptin is mainly produced by white adipose tissue. Leptin blood level is proportional to body fat. The more body fat on the body the more leptin that is produced.

• Differences in brain activity during eating in people with leptin deficiency and those with normal leptin levels.
  

• When leptin is given to genetically obese mice they lose 30% of their body weight in 2 weeks. When leptin is given to lean mice they lost all their body fat in 4 days.
  

• Human trials with leptin were unsuccessful. Except at the highest doses (several tablespoons a day) there were no significant changes in weight.

• Why was it so unsuccesful? Obese humans develop a resistancy to leptin in their brain.

Explaining and Reversing Leptin Resistance

• Umut Ozcan - Harvard - Endoplasmic Reticulum Stress Plays a Central Role in Development of Leptin Resistance

• General Hypothesis: The hypothalamus has become resistant to leptin through a process called Endoplasmic Reticulum Stress (ER Stress) which ultimately results in reduced ER function. This causes reduced function of Leptin Receptor signaling. To resensitize the brain to leptin it is necessary to improve function in the ER. Chemical chaperones have been shown to do this.

• The Endoplasmic Reticulum is an organelle responsible for protein folding and transportation of proteins to the cell membrane.

• If the normal processes of the ER are disturbed misfolded proteins accumulate in the cell. This activates cellular stress mechanism called the Unfolded Protein Response (UPR) is activated.

• UPR halts protein translation and causes an increase in the production of molecular chaperones involved in protein folding. If this mechanism is unsuccessful, UPR leads to apoptosis.
  

• How ER stress is induced and how this leads to UPR is not well understood. The main theory suggests that increased levels of circulating cytokines, fatty acids, excess nutrition and activation of the rapamycin pathway (involved in cellular homeostasis) contribute.
  

• What they demonstrated in the paper:

1. Leptin Acts on a Subset of Hypothalamic neurons
2. ER Stress Inhibits Leptin Receptor Signaling
3. ER Stress Creates Leptin Resistance in the Brain of Lean Mice
4. Improvement of ER Function Enhances Leptin Signaling
5. ER Capacity of the Brain Links Obesity to Leptin Resistance
6. Chemical Chaperones are Leptin Sensitizers.

2. ER Stress Inhibits Leptin Receptor Signaling

• Cells that presented the Leptin Receptor (LepRB) were exposed to tunicamycin (a chemical that induces ER stress) and then treated with leptin for 45 minutes.

• There was no evidence of leptin-stimulated tyrosine phosphorylation of LepRB or Stat3 phosphorylation (both cellular events that occur as a result of leptin binding to LepRB).

• This indicates that UPR inhibits LepRB signaling at all steps.

• Since LepRB is folded in the ER they next investigated ER stress blocks LepRB translocation from the ER to the cell membrane as a possible explanation of the block in leptin signaling.

• They induced ER stress in cells using tunicamycin and then used immunflorescence staining to analyze LepRB levels in the cell membrane. They found that ER stress does not decrease LepRB translocation to the membrane nor does it cause a misfolding of LepRB.

3. ER Stress Creates Leptin Resistance in the Brain of Lean Mice

• First - Showed that injecting tunicamycin into the hypothalamus of lean mice caused ER Stress.

• Second - Showed that ER stress in the brain's of lean mice completely blocked activation of Stat3.

• Third - Noted that the food uptake of lean mice with induced ER stress in the hypothalamuc increased.

5. ER Capacity of the Brain Links Obesity to Leptin Resistance

• Bred XNKO mice that produced less of the regulators involved in protein folding in the ER therefore making them more susceptible to ER stress (deletion of the XPB1 gene).

• On a normal diet they had a slightly lower body weight. Blood glucose and leptin levels were normal. Glucose homeostasis was maintained within a normal range.

• On a high fat diet the XNKO mice gained weight more quickly. A sharp increase in leptin level was maintained through out the experiment. They consumed more food, had a higher total fat amount and a significantly lower lean mass.

• These results support the hypothesis that ER capacity of the brain is involved in regulating body weight, leptin sensitivity and metabolic homeostasis.

6. Chemical Chaperones are Leptin Sensitizers

• Chemical chaperones are compounds that have been found to increase ER function and decrease the accumulation of misfolded proteins in the ER, thereby reducing the likelihood that ER stress will occur.
  

• 2 FDA approved chemical chaperones for humans are 4-phenyl butyrate (PBA) and tauroursodeoxycholic acid (TUDCA). Past studies have shown that these chemicals can relieve ER stress in the liver and adipose tissues, as well as enhancing insulin sensitivity in mouse models.
  

• Attempted to reverse ER stress in the hypothalamus of mice who had been on a high fat diet. Normal mice were kept on a high-fat diet for 25 weeks and then treated with PBA for 10 days, followed by daily leptin administration.
  

• Control mice rapidly lost weight and then rapidly regained it. Mice treated with PBA rapidly loss weight, they also consumed less food.

• Similar results were obtained with TUDCA.
  

• Both PBA and TUDCA also had some success in increasing leptin sensitivity in genetically obese mice (ob/ob mice).

What This Means

• After years of searching for leptin-sensitizing agents, chemical chaperones have been identified as potential novel treatment options for obesity.

Music evokes emotion in children with autism

Here's my article.


Music and Autism

Musical Behavior in a Neurogenetic Developmental Disorder

Evidence from Williams Syndrome

Daniel J. Levitin

Daniel J. Levitin's paper reviews a series of studies performed to assess the musical abilities and behaviors of individuals with Williams Syndrome- a neurogenetic developmental disorder.

What is Williams Syndrome (WS)?

Williams Syndrome is created by a small genetic accident which occurs during meiosis, when a segment of DNA containing 25 genes is lost. The result of which affects abstract thought, so that many WS have a bad concept of spacial, quantitative, reasoning, attention, eye-hand coorination, and reading abilities. WS people tend to be very talkative, and will talk with everyone; they completely lack a sense of social fear. Functional brain scans have shown that the amygdala in WS people shows no reaction when they see angry or worried faces.

Here is an image taken from the National Institutes of Health website depicting the difference in amydala activity scanned in reaction to threatening scenes and faces in WS participants and controls (http://www.nih.gov/news/pr/jul2005/nimh-10.htm)

Abnormal regulation of the amygdala in participants with Williams Syndrome (right) compared to controls (left). The amygdala activates more for threatening scenes (bottom), but less for threatening faces (top).

What is the connection between WS and music?
Not only do WS people show extreme friendliness and near-normal speaking skills, they also tend to be more engaged in musical activities and musicality than others. Levitin reports in this paper a possible neuroanatomical correlate of this engagement, with increased activation in the right amydala to music and to noise.

Based on Levitin and his team's observations, claims of musicality involve many aspects of music including frequent music listening, music performance (for example: a WS person can be able to play the clarinet despite not knowing how to tie their shows) , a deep emotional engagement with msuic, or an above-average musical memory and sound sensitivities (hyperacusis) involving unusual sensitivity to sound, categorization or labelling of sounds that others can't, or anxiety and fear of sounds that non-WS people do not find aversive.

Levitin says that WS can help us better understand the links between genes, brain, and musical behaviors and that WS hypersociability and lack of social inhibitions might be related to their musicality.

The Studies

1st Step:
Characterizing the musical phenotype in WS
The Questionnaire.
Levitin administered a questionnaire to the caregivers of 130 WS participants, 130 Down syndrome participants, 130 autistic participants, and to 130 normal controls. The questionnaire gathered information about physical variables, interest in music, emotional responses to music, musical training, the amount of time engaged in musical activities, and the age of onset of musical activities.

Individuals with WS showed a significantly younger age of onset of musical interest, spent more time per week listenign and playing, and were reported to experience higher levels of emotion when listening to music.

A prinical components analysis revealed seven underlying orthogonal factors that contributed to the profile obtained from the questionnaire. This can be divided up into 7 factors including content related to musical complexity, reproduction, sensitivity, musical theory and achievement, listening habits, positivity, and emotions.

Study of Neural Correlates of Auditory Perception in WS using fMRI

Levitin hypothesized that he would find differences in brain activation bewteen people with WS and controls, and that WS people would show a wider and more diffuse pattern of activation to music and noise stimuli than controls, and that they would show a greater amygdaloidal activation, indexing their heightened emotional reations to music and noise.

Study was conducted usuing a desensitization program that involved a professionally proudced video introdcution to the fMRI scanning procedure, usuing a child's-eye-view of the facility and a child's narration. This was followed to a visit fo an fMRI simulator in which the participants could become acclimated to the noises and enclosed space. 5 WS participants were recruited for an fMRI study of differential processing of music and noise, and five age- and sex-matched controls.
Participants listened to to excerpts from familiar and unfamiliar classical music, as well as the types of noisy sounds that WS people are often sensitive to, such as fans, motors, and leaf blowers.

Results:

Comparing music to noise, WS individuals showed a significantly lower voxel intensity bilaterally in the superior temporal cortex, middle temporal gyri, and superior temporal sulcus. In a comparison of responses to music-minus-rest vs. noise-minus-rest, control participants showed significantly higher temporal lobe activations to the music than the noise, while the WS participants showed virtually indistinguishable activation levels.

He also observed marked differences between WS patients and controls in the right amydala, with WS patients exhibiting far greater activation intensity in the music-minus-noise contrast. This points to a possible neural basis for the unusal acoustical and musical sensitivities observed in affected individuals. Overall, WS participants showed more variable and diffuse activations throughout the brain, and the showed increased activation in the amygdala and cerebellum.

The test of musical skills:

Rhythmic Production Ability

To test rhthym, Levitin and his team presented 8 WS individuals and 8 mentally age-matched controls with a set of clapped rhythums in increasing complexity. The participant had to clap back the rhythm as accurately as possible. Independent coders, blind to hypothesis, and group membership, analyized audio tapes of the test sessions and scored each trial as correct or incorrect or incorrect but very musical nonetheless.

The results showed that the WS and control participants obtained an equal number of correct trials about 66%. However, WS indiviuduals were three times more likely when incorrect to supply a musically compatible rhythm. This was interpreted as a marker of rhythmic ability or creative rhythmicity among the WS participants.

Melodic Production Ability

Levitin presented 12 WS individuals, 12 chronologically age-matched NCs, and 12 individuals with DS a set of melodies increasing in complexity, to assess their melodic reproduction ability. WS and NC were statistically better at melodic repetition than the DS, and not significantly different from one another. He then presented all participants with a set of melodic fragments and instructed them to complete the melodies. The WS individuals were not as good at melodic completion as the NCs. Thus, WS individuals are better at rhymic production than melodic production.

Sources:

Levitin, Daniel J.  (2005) Musical Behavior in a Neurogenetic Developmental Disorder, Retrieved March 15, 2009 from Daniel J. Levitin's Website: http://www.psych.mcgill.ca/levitin/

Dobbs, David "The Gregarious Brain." The New York Times July 8, 2007. Retrieved on March 15, 2009 from nytimes.com

Obesity: Reviving the Promise of Leptin

Hi everyone,

Here's the link to my article: Obesity: Reviving the Promise of Leptin

Musical Behavior in a Neurogenetic Developmental Disorder

Here is the link to the article by Daniel J. Levitin:

http://ego.psych.mcgill.ca/labs/levitin/research/MusicalBehaviorNeuro.pdf

And here is a link to a NYtimes article which explains Williams syndrome:

http://www.nytimes.com/2007/07/08/magazine/08sociability-t.html

Medial Prefrontal Cortex Links Music, Memory, and Emotion

In a study at UC Davis, Petr Janata mapped the areas of the brain that responded to clips of familiar music, to explore the locations that play a role in the integration of music and autobiographical memories. The area he established as the “hub” that links familiar music, memories, and emotions is the medial prefrontal cortex (MPFC), already understood to be where memories are “supported and retrieved.”

Janata based his hypothesis that the MPFC would be at the center of activity on several previous studies that showed it to be involved in autobiographical memory retrieval. In several of his own earlier studies, Janata had observed that the MPFC is used to track music through tonal space, and that music serves as a powerful retrieval cue for autobiographical memories. Another compelling study showed that the MPFC atrophies more slowly than other brain areas in patients with Alzheimer’s disease, and that memory for familiar music is something that these patients retain longer than many other memories.



There were two hypotheses being tested in this experiment: the first is that activity in the MPFC would show positive correlation to the familiarity, autobiographical salience, and positive affect brought about by the music. The second was that overlapping areas, of those in close proximity to those demonstrating positive correlation, would track the musical excerpts through tonal space. For the sake of time, I will address the first hypothesis.

Method:
Janata’s study involved 13 students at UC Davis. Using songs from the Top 100 charts from when the subjects were between 7 and 19 (to ensure there would be some familiarity with the songs), Janata used fMRI scans to monitor their brains while they listened to 30 second excerpts from 30 different songs.

Following each excerpt, subjects pressed buttons on a keypad to respond to questions about the valence (how pleasant the music was) and arousal while listening to the clip, their familiarity with the song, whether it held any particular autobiographical associations for them, the orientation of their attention to those associations/memories, and the orientation of their attention to the music itself. After the fMRI monitoring, subjects completed a survey about the memories they had experienced while listening to the song excerpts.

Results:
From the 17 songs that the subjects remembered on average, 13 had moderate to strong associations to autobiographical memories. Songs that had the strongest associations also evoked the most emotional, vivid responses. In the fMRI images, these memories corresponded to activity in the upper part of the MPFC.


This shows the results of the ratings the subjects assigned to each song excerpt. Black represents the most negative value for each scale, and white represents the most positive.




Abbreviations: STG, superior temporal gyrus; DLPFC, dorsolateral prefrontal cortex; DMPFC, dorsomedial prefrontal cortex; VLPFC, ventrolateral prefrontal cortex; VMPFC, ventromedial prefrontal cortex; IFG, inferior frontal gyrus; FO, frontal operculum; IPS, intraparietal sulcus; AG, angular gyrus; pSMA, presupplementary motor area; ACC, anterior cingulate cortex; PCC, posterior cingulate cortex; IFS, inferior frontal sulcus; MFG, middle frontal gyrus; Ins, insula; SPL, superior parietal lobule; Cb, cerebellum; PT, planum temporale; vltn, ventral lateral thalamic nucleus; and MTG, middle temporal gyrus.

In these images, you can see brain activity during different phases of the experiment: music playing, question-answer period, and the effects of familiarity, autobiographical salience, and valence. FAV represents “the combined effects of hearing pleasing, familiar, and autobiographically salient songs relative to unfamiliar, emotionally neutral, or displeasing songs that elicited no autobiographical association.” These images show the concentration of activity related to associations in the prefrontal cortex, as well as the left-hemispheric bias (the negative numbers refer to the left hemisphere).




In this second set of images, you can see the individual effects of familiarity, autobiographical salience, and valence, showing the same trends as the first set of images.


Implications:
Janata’s results show that the MPFC is key in associating familiar music with autobiographical memories. Importantly, it links structural characteristics of a retrieval cue with episodic memories (in spontaneous, rather than effortful, retrieval). This builds on existing knowledge of autobiographical memory by demonstrating the “spontaneous activation of an autobiographical memory network in a naturalistic task with low retrieval demands.”

Although Janata’s study itself did not suggest the uses or applications of this discovery, he is quoted in the ScienceDaily article as saying that a long-term goal for this new knowledge was to use music to improve Alzheimer’s patients’ quality of life.



Sources:
Janata, P. (2009). The Neural Architecture of Music-Evoked Autobiographical Memories. Retrieved February 24, 2009, from Cerebral Cortex Website: http://cercor.oxfordjournals.org/cgi/content/full/bhp008v1#ABS

Nervous System. Retreived March 1, 2009, from A Review of the Universe Web site: http://universe-review.ca/R10-16-ANS.htm

University of California - Davis (2009, February 24). Brain Hub That Links Music, Memory And Emotion Discovered. Retrieved February 24, 2009, from Science Daily Web site: http://www.sciencedaily.com/releases/2009/02/090223221230.htm

Imaging Study on Women with Anorexia Nervosa

"Sense of Taste Different
in Women with Anorexia Nervosa" 
Imaging Study Finds Brain Changes Associated with the Regulation of Appetite .
September 25, 2007
By Debra Kain

Although anorexia nervosa is categorized as an eating disorder, it is not known whether there are alterations of the portions of the brain that regulate appetite. Now, a new study finds that women with anorexia have distinct differences in the insula – the specific part of the brain that is important for recognizing taste – according to a new study by University of Pittsburgh and University of California, San Diego researchers currently on line in advance of publication in the journal Neuropsychopharmacology. The study also implies that there may be differences in the processing of information related to self-awareness in recovering anorexics compared to those without the illness – findings that may lead to a better understanding of the cause of this serious and sometimes fatal mental disorder. In the study led by Angela Wagner, M.D., University of Pittsburgh School of Medicine, and Walter H. Kaye, M.D., of the University of Pittsburgh and the University of California, San Diego (UCSD) Schools of Medicine, the brain activity of 32 women was measured using functional magnetic resonance imaging (fMRI.) The research team looked at images of the brains of 16 women who had recovered from anorexia nervosa – some of whom had been treated at the Center for Overcoming Problem Eating at Western Psychiatric Institute and Clinic of the University of Pittsburgh Medical Center –and 16 control subjects. They measured their brains’ reactions to pleasant taste (sucrose) and neutral taste (distilled water.)
The results of the fMRI study are the first evidence that individuals with anorexia process taste in a different way than those without the eating disorder. In response to both the sucrose and water, imaging results showed that women who had recovered from anorexia had significantly reduced response in the insula and related brain regions when compared to the control group. These areas of the brain recognize taste and judge how rewarding that taste is to the person. In addition, while the controls showed a strong relationship between how they judged the pleasantness of the taste and the activity of the insula, this relationship was not seen in those who had recovered from anorexia. According to Kaye, it is possible that individuals with anorexia have difficulty recognizing taste, or responding to the pleasure associated with food. Because this region of the brain also contributes to emotional regulation, it may be that food is aversive, rather than rewarding. This could shed light on why individuals with anorexia avoid normally “pleasurable” foods, fail to appropriately respond to hunger and are able to lose so much weight. “We know that the insula and the connected regions are thought to play an important role in interoceptive information, which determines how the individual senses the physiological condition of the entire body,” said Kaye. “Interoception has long been thought to be critical for self-awareness because it provides the link between thinking and mood, and the current body state.” This lack of interoceptive awareness may contribute to other symptoms of anorexia nervosa such as distorted body image, lack of recognition of the symptoms of malnutrition and diminished motivation to change, according to Kaye. Anorexia nervosa is a serious and potentially lethal illness, which may result in death in ten percent of cases. Anorexia commonly begins during adolescence, but strikes throughout the lifespan, and is nine times more common in females than in males. These characteristics support the possibility that biological processes contribute to developing this disorder.


Why does this study hold significance?

Anorexia Nervosa is a disorder of unknown etiology. The stigma that has lastingly attached itself to the disease supports that psychological reasons are responsible for the birth of the disorder. Despite this, it is being questioned whether individuals afflicted with anorexia, have a primary disturbance of pathways that modulate feeding, or if disturbed appetite is secondary to psychological elements of the disease such as anxiety, and an obsession with weight gain. Through this case study, we are able to see that the controlled women acknowledged a pleasant relationship with the ingestion of sucrose and their signal activity supported that as well. Conversely, the recovered anorexics of this study possessed no relationship between the pleasantness of sugar’s taste and any brain region. Both groups showed no anxiety or pleasantness of the taste of water in relation to any brain region. These results support the hypothesis that recovered anorexics have disturbances in their taste processing via the central nervous system. We see that the insula can assert the value of taste stimuli and consequently influence how that stimuli affect’s the state of the human body. If an anorexic cannot distinguish her feelings towards particular foods—if she experiences no neurological reward or taste value—it is easier for her to fall into disordered eating habits, especially if she has psychological instabilities that would only strengthen her resistance to food. Essentially, this study was the first of its kind in showing that there is a disturbance in the insula and other primary taste regions of the brain in anorexics, which in turn can help professionals potentially treat Anorexia Nervosa in a more inclusive way.

http://www.nytimes.com/2007/02/06/health/psychology/06brain.html

The link above has a more specified article on the insula, and an interesting diagram to match, if anyone wants more background information on the insula.

Other Sources:

www.neuropyschopharmacology.org
"The Mind Has a Body of its Own," by Sandra and Matthew Blakeslee.

Oxytocin and Generosity

The Study:

The study attempted to connect the neuromodulator oxytocin with increased generosity by showing that it increases perspective-taking or empathy.

To isolate oxytocin’s impact on perspective-taking, the researchers used two money transfer tasks, the Ultimatum Game and the Dictator Game

In both tasks, participants were randomly assigned to pairs, but did not have the opportunity to see or converse with their partners. One member of the pair (referred to as Decision Maker 1, in the study, but referred to here as the Giver) was given $10. The other member of the pair (referred to in the study as Decision Maker 2, but referred to here as the Receiver) received no money at the start of the game.

Ultimatum Game: In the Ultimatum Game, the Giver was asked to choose an amount of money to transfer to the Receiver. If the Receiver accepted the transfer, both partners got the agreed-upon amounts of money. If, on the other hand, the Receiver rejected the offer as too stingy, neither partner kept any money. The Giver only had the opportunity to make one offer and could not renegotiate.

Dictator Game: In the Dictator Game, the Receiver had to accept whatever amount of money was given to him by the Giver.

The Ultimatum Game differs from the Dictator Game in that, in order to succeed at the task, the Giver must think about what the Receiver will do. The researchers encouraged this by asking all participants, before they were assigned to particular roles, to think about both the amount they would transfer as a Giver and the minimum amount they would accept as a Receiver. In the Dictator Game, the Giver does not need to explicitly think about the Receiver, but instead “simply decides how much one would like to give up.”

Before completing these tasks, half of the participants were infused intranasally with oxytocin and the other half were given an intranasal placebo to see what effect oxytocin would have on decision-making in the two games.

The Results:

As the researchers predicted, oxytocin increased the magnitude of transfers in the Ultimatum Game, but not in the Dictator Game. Only when participants had to think about another person did oxytocin affect they amount they were willing to give. Participants who had received oxytocin gave 21% more as Givers in the Ultimatum Game than those who had received the placebo.

The average transfers in the Ultimatum Game were $4.86 for the oxytocin group and $4.03 for the control group.

The researchers distinguished between generosity and altruism.

Generosity: Liberality in giving. Offering more to another than he or she expects.
Altruism: Helping another at a cost to oneself.

The Ultimatum Game most nearly tests generosity, since it compares the amounts a person is willing to give to an amount that is expected, while the Dictator Game most nearly tests altruism, since it measures how much of a cost to oneself one is willing to endure, without any particular mark of comparison.

In the Ultimatum Game, significant generosity is shown by participants who have taken oxytocin, meaning that these participants gave more than the average amount that people would be willing to accept as a Receiver. Those who had taken oxytocin were 80% more generous.


From this, the researchers concluded that oxcytocin increases generosity, but not altruism, by increasing participants’ ability to take on the perspective of another person. The researchers hypothesized that when participants in the oxytocin group thought about the Receiver while acting as Giver in the Ultimatum Game, they identified more strongly with the disappointment and negative emotions that the Reciever would feel if the transfer was small, and so they gave larger amounts. The paper states, “OT [oxytocin] appeared to have selectively affected the understanding of how another would experience a negative emotion, and seemed to have motivated a desire to reduce DM2s’ [Receivers’] experienced negativity. This could be called empathy.”

An Alternative Reading of the Data:

Another explanation for the effects of oxytocin in the Ultimatum Game could be that oxytocin decreases risk-taking behavior. Givers who have received oxytocin might give more because they prefer to secure a smaller amount for themselves than to risk having their offer rejected and getting nothing. This explanation is not likely, however, because oxytocin did not have any effect on the minimum offer that participants were willing to accept as Receiver. If oxytocin led to risk-aversion, Receivers would also be willing to accept smaller, secure amounts, rather than sticking to a higher acceptance threshold. Also, another experiment, primarily designed to study the effects of oxytocin on trust levels, showed that oxytocin does not affect risk-taking.

Calling Out Discover:

The end of the Discover article raises the spectre of casinos filling the air with oxytocin to make people gamble more. As I just stated, the actual study suggests no link between oxytocin and risk-taking. The increased payouts in the study occurred only when participants were induced to actively think about the person who would benefit from their giving. This would be helpful to casinos only if people pulling the slot machine considered how the casino owner would feel about receiving their money—an unlikely scenario. The Discover comment is purely sensationalist.

What is Oxytocin Anyhow?

Oxytocin is a neuromodulator which is primarily known for its involvement in female reproduction. It is critical to birth and breastfeeding. Recent research has discovered that it is also very important in regulating social interactions. One study showed that mice with a mutant gene that prevented them developing oxytocin receptors lacked social memory. The connection between oxytocin and sociality is supported by the fact that areas of the brain that deal with emotions and social behavior tend to have more oxytocin receptors. These areas include the amygdala, hypothalamus, and anterior cingulate.

fMRI Evidence:

In a recent study, participants decided whether or not to make donations to social causes while undergoing an fMRI. The study found that, when participants chose to make donations, the mesolimbic-striatal reward system was activated in the same way as when participants were given monetary rewards. This accounts in part for the positive feelings associated with giving. In addition, participants making donations showed activation in the subgenual area (including Brodmann’s area 25) which was not activated while receiving money. This area is important in social attachment and affiliation. It is also involved in the release of oxytocin, suggesting that oxytocin has an effect on making decisions about donations. This reinforces the link between oxytocin and generosity.


(a) Mesolimbic–striatal reward system, including the VTA and the dorsal and ventral sectors of the striatum (STR), activation for both pure monetary reward and noncostly donation (conjunction of pure reward vs. baseline and noncostly donation vs. baseline). (b) Subgenual area (SG) activation for decisions to donate (conjunction of costly and noncostly conditions) as compared with pure monetary reward. The subgenual area comprised the most posterior sector of the medial orbitofrontal cortex and the ventral cingulate cortex (BA 25) and the adjoining septal region structures. (Caption taken from Moll, J., et. al.)


Area 25 was activated during the donation task, and is involved in the release of oxytocin.

Another study examined the effects of oxytocin on the amygdala. Participants were given either oxytocin or a placebo intranasally. Then, while undergoing an fMRI scan, they viewed angry and fearful faces and threatening scenes. For those who had received the placebo, this caused a large amount of activation in the amygdala. Those who had received oxytocin showed significantly less activation in the amygdala, suggesting that oxytocin can interfere with fear responses. The authors of “Oxytocin Increases Generosity in Humans” suggest that interference with the amygdala by oxytocin may make people less anxious about resource scarcity, and therefore more likely to give larger amounts in the Ultimatum Game. Another study has shown that oxytocin increases people’s willingness to trust strangers. This effect could be attributed to decreased activity in the amygdala inhibiting normal fear of betrayal.

Significance:

As the role of oxytocin in regulating social behavior comes to be better understood, it could be involved in new treatments of social disorders. The connection between oxytocin and perspective-taking indicated by this study may be of particular importance to autism researchers.

Sources:

Barone, J (2008) Can the hormone oxytocin drive us to be more generous? Discover. Retreived February 21, 2009, from http://discovermagazine.com/2008/apr/04-a-dose-of-human-kindness-now-in-chemical-form

Ferguson JN, Young LJ, Hearn EF, Matzuk MM, Insel TR, Winslow JT (2000) Social amnesia in mice lacking the oxytocin gene. Nat Genet 25: 284–298.
Kosfeld M, Heinrichs M, Zak PJ, Fischbacher U, Fehr E (2005) Oxytocin increases trust in humans. Nature 435: 673–676.

Moll J, Krueger F, Zahn R, Pardini M, de Oliveira-Souza R, Grafman J (2006) Human fronto–mesolimbic networks guide decisions about charitable donation. Proc Nat Acad Sci 103: 15623–15628.

National Institute of Mental Health (2005) Trust-building hormone short-circuits fear in humans. Retrieved February 21, 2009, from http://www.nih.gov/news/pr/dec2005/nimh-07.htm

Zak PJ, Stanton AA, Ahmadi S (2007) Oxytocin Increases Generosity in Humans. PLoS ONE 2(11): e1128. doi:10.1371/journal.pone.0001128